Nicotine pouch

ABSTRACT

The disclosure provides chewable nicotine formulations comprising an orally-acceptable nicotine salt, an orally-acceptable alcohol, flavor components, and an orally-acceptable binder in a water-permeable, water-insoluble pouch, together with methods of making and using the same.

FIELD

This disclosure relates to chewable pouch products comprising nicotinein free base and salt form, together with methods of making and usingthe same.

BACKGROUND

The health hazards of smoking are well-established. Products which candeliver nicotine via the oral mucosa rather than via the lungs includesnuff, snus, chewing tobacco, nicotine chewing gums, and oral pouchescomprising nicotine. These products face challenges in manufacturing,shelf stability, efficient nicotine delivery, and consumer acceptance.Nicotine is readily oxidized, so to enhance shelf stability, nicotinebase may be stabilized in a polymer or gum matrix or provided in saltform. Nicotine free base is believed to be better absorbed through theoral mucosa than nicotine salts, so products which provide nicotine insalt form may further comprise pH-adjusting agents to raise the oral pHupon use, thereby releasing the free base. High pH products may haveundesirable bitter or soapy flavors, and/or poor mouthfeel, whileproducts where nicotine is polymer-stabilized may release nicotinerelatively slowly and inefficiently. The disadvantages of these chewableproducts may make them unappealing to users as an alternative tosmoking, even though products that deliver nicotine by smoking maypresent greater danger to the heart and lungs than chewable products.

There is a need for chewable nicotine delivery products, which releasenicotine quickly and efficiently, have good flavor and mouthfeel, andwhich are stable for long-term storage.

SUMMARY

The disclosure provides a chewable nicotine product, comprising nicotinebase, nicotine salt, flavor, and binder in a water-permeable,water-insoluble pouch, wherein nicotine and flavor are released when thepouch is chewed, and wherein the product provides good nicotine release,flavor, mouthfeel, and shelf-stability.

For example, in one embodiment, the disclosure provides a chewablenicotine formulation comprising nicotine, an orally-acceptable nicotinesalt, an orally-acceptable alcohol, flavor components, and binder in awater-permeable, water-insoluble pouch.

In another embodiment, the disclosure provides a method for making apouch comprising nicotine, nicotine acid addition salt, propyleneglycol, flavor, and binder, wherein the nicotine acid addition salt isformulated in nonaqueous conditions, using propylene glycol as solvent,and products made thereby.

In another embodiment, the disclosure provides a method of deliveringnicotine, for example a method of nicotine replacement therapy,comprising administering the above-described chewable pouch to a subjectin need thereof.

Further areas of applicability of the present disclosure will becomeapparent from the detailed description provided hereinafter. It shouldbe understood that the detailed description and specific examples, whileindicating certain preferred embodiments of the disclosure, are intendedfor purposes of illustration only and are not intended to limit thescope of the disclosure.

DETAILED DESCRIPTION

The formulations of the disclosure are non-aqueous formulations,comprising nicotine and orally-acceptable acid to form a nicotine acidaddition salt in an orally-acceptable alcohol solvent (e.g., propyleneglycol), together with flavor and binder, in a water-permeable,water-insoluble pouch. Alcohols, such as propylene glycol, have a muchlower dielectric constant than water, so the nicotine andorally-acceptable acid dissolved in the alcohol do not produce ions tothe same extent as they would in water, which has unpredictable effectson salt formation, relative to salt formation in aqueous solution. It isfound that the nicotine acid addition salt provided thereby is stablerelative to nicotine in entirely free base form, but also provides abetter mouth feel and nicotine delivery than a nicotine salt formed inaqueous solution.

In a first embodiment, the disclosure provides a chewable nicotineformulation comprising nicotine, an orally-acceptable nicotine salt, anorally-acceptable alcohol, flavor components, and an orally-acceptablebinder in a water-permeable, water-insoluble pouch (Formulation 1). Forexample, the disclosure provides the following formulations:

-   -   1.1. Formulation 1 wherein the orally-acceptable nicotine salt        is selected from nicotine hydrochloride, nicotine        dihydrochloride, nicotine monotartrate, nicotine bitartrate,        nicotine sulphate, nicotine zinc chloride monohydrate, nicotine        pyruvate, nicotine phosphate, nicotine salicylate, nicotine        malate, nicotine carbonate, nicotine bicarbonate, nicotine        acetate, nicotine citrate, nicotine folate, nicotine fumarate,        nicotine lactate, and nicotine benzoate.    -   1.2. Any foregoing formulation wherein the orally-acceptable        nicotine salt is a salt of an orally-acceptable organic acid.    -   1.3. Any foregoing formulation wherein the orally-acceptable        nicotine salt is a salt of an orally-acceptable monoprotic        organic acid.    -   1.4. Any foregoing formulation wherein the orally-acceptable        nicotine salt is nicotine benzoate.    -   1.5. Any foregoing formulation wherein the molar ratio between        nicotine free base and orally-acceptable nicotine salt is 1:1 to        1:10.    -   1.6. Any foregoing formulation wherein the molar ratio between        nicotine free base and nicotine acid addition salt is about 1:2.    -   1.7. Any foregoing formulation wherein the formulation comprises        an orally-acceptable acid, e.g., selected from hydrochloric        acid, tartaric acid, pyruvic acid, phosphoric acid, salicylic        acid, malic acid, carbonic acid, acetic acid, citric acid,        tartaric acid, folic acid, fumaric acid, lactic acid, and        benzoic acids; e.g., benzoic acid.    -   1.8. Any foregoing formulation wherein the orally-acceptable        alcohol is propylene glycol.    -   1.9. Any foregoing formulation wherein the binder is selected        from polysaccharides, polyols, sugars, natural fibers,        microcrystalline cellulose, cellulose and cellulose derivatives,        and mixtures thereof.    -   1.10. Any foregoing formulation wherein the binder is a        hydroscopic but insoluble material.    -   1.11. Any foregoing formulation wherein the binder comprises        microcrystalline cellulose.    -   1.12. Any foregoing formulation wherein the water-permeable,        water insoluble pouch is made of a semi-permeable material which        substantially prevents the binder from leaving the bag but        permits saliva and therein dissolved components from the powder        in the pouch to freely pass through said material.    -   1.13. Any foregoing formulation wherein the water-permeable,        water insoluble pouch is made from one or more polymers or        fibers safe for oral use, e.g., selected from polypropylene, low        density polyethylene, polyethylene terephthalate, polyurethane,        polyvinyl acetate, polyvinyl alcohol, polystyrene,        poly(ethylene-vinyl acetate), rayon, silk, cotton, polyester,        cellulosic materials (e.g., hydroxypropyl cellulose), and        combinations thereof.    -   1.14. Any foregoing formulation further comprising one or more        additional components selected from antioxidants, emulsifiers,        preservatives, and solvents.    -   1.15. Any foregoing formulation further comprising a neutral,        orally-acceptable mineral salt, e.g., selected from sodium        chloride, potassium chloride, and mixtures thereof, e.g.,        comprising potassium chloride.    -   1.16. Any foregoing formulation which is substantially free of        any basic ingredient other than nicotine.    -   1.17. Any foregoing formulation which is substantially free of        water.    -   1.18. Any foregoing formulation which is made under        substantially water-free conditions.    -   1.19. Any foregoing formulation, wherein the contents of the        water-permeable, water-insoluble pouch have a pH of less than 7,        e.g., pH 5.5 to pH 6.9, e.g., about pH 6.5, when measured in a        10% slurry in water.    -   1.20. Any foregoing formulation, wherein the ratio by weight        of (i) binder and (if present) neutral orally-acceptable mineral        salt, e.g., potassium chloride, to (ii) nicotine,        orally-acceptable nicotine salt, orally-acceptable alcohol, and        flavor, is from 70:30 from 50:50, e.g., 65:35 to 55:45, e.g.        about 60:40.    -   1.21. Any foregoing formulation wherein the orally-acceptable        nicotine salt is nicotine benzoate, the orally-acceptable        alcohol is propylene glycol, and the orally-acceptable binder is        microcrystalline cellulose.    -   1.22. Any foregoing formulation wherein the contents of the        water-permeable, water-insoluble pouch consist of nicotine,        nicotine benzoate, potassium chloride, propylene glycol, flavor,        and binder.    -   1.23. Any foregoing formulation wherein the contents of the        water-permeable, water-insoluble pouch consist of nicotine,        nicotine benzoate, potassium chloride, propylene glycol, flavor,        and microcrystalline cellulose.    -   1.24. Any foregoing formulation wherein the flavor components        are pH neutral.    -   1.25. Any foregoing formulation wherein the flavor components        comprises one or more flavors selected from mint oil, menthol,        watermelon, blueberry, pomegranate, strawberry, blueberry,        dragonfruit, and cucumber flavors.    -   1.26. Any foregoing formulation wherein the flavor components        comprise mint oil and/or menthol.    -   1.27. Any foregoing formulation wherein the nicotine comprises        synthetic nicotine. 1.28. Any foregoing formulation wherein the        nicotine comprises nicotine from tobacco. 1.29. Any foregoing        formulation wherein the nicotine has an (R):(S) isomeric ratio        of greater than 1.    -   1.30. Any foregoing formulation wherein the contents of the        water-permeable, water-insoluble pouch are in dry powder form.    -   1.31. Any foregoing formulation comprising 1%-9%, e.g. 2-5%,        e.g., 2.5-3.5%, of nicotine and orally-acceptable nicotine        salts, by weight of the contents of the water-permeable,        water-insoluble pouch.    -   1.32. Any foregoing formulation comprising 4-20%, e.g., 5%-15%,        e.g., about 5%, or or about 10%, or about 15%, of        orally-acceptable alcohol, e.g. propylene glycol, by weight of        the contents of the water-permeable, water-insoluble pouch.    -   1.33. Any foregoing formulation comprising 50%-70%, e.g.        55%-60%, of binder, e.g., microcrystalline cellulose, by weight        of the contents of the water-permeable, water-insoluble pouch.    -   1.34. Any foregoing formulation comprising 0.5%-2%, e.g.,        1%-1.5%, of orally-acceptable mineral salt, e.g. potassium        chloride, by weight of the contents of the water-permeable,        water-insoluble pouch.    -   1.35. Any foregoing formulation wherein the contents of the        water-permeable, water-insoluble pouch comprise:        -   Nicotine: 1% to 6%, e.g. 1% to 3%, e.g., 2%        -   Benzoic acid: 0.5% to 3%, e.g., 0.5% to 1.5%, e.g., 1%        -   Propylene glycol: 5% to 20%        -   Flavor: 20% to 35%        -   Microcrystalline cellulose: 55% to 60%        -   Potassium chloride: 1% to 1.5%        -   wherein all amounts are by weight of the contents of the            pouch,        -   wherein the nicotine and benzoic acid may be in free or salt            form or mixtures thereof, and        -   wherein the weight of the nicotine is calculated as the free            base equivalent and the weight of the benzoic acid is            calculated as the free acid equivalent, irrespective of the            actual proportions of nicotine and benzoic acid in free or            salt form.    -   1.36. Formulation 1.35 wherein the weight percent of the solid        components comprising microcrystalline cellulose and potassium        fluoride is 55% to 65%, e.g., about 60%; and the weight percent        of the liquid components comprising propylene glycol, nicotine,        benzoic acid and flavor is 35% to 45%, e.g., about 40%.    -   1.37. Formulation 1.35 or 1.36 wherein the weight ratio of        nicotine to benzoic acid is 1:1 to 3:1, e.g., about 2:1.    -   1.38. Formulation 1.35, 1.36 or 1.37 wherein the molar ratio of        nicotine to benzoic acid is 3:1 to 1:3, e.g., from 2:1 to 1:1,        e.g., is about 3:2.    -   1.39. Any foregoing formulation wherein each pouch contains a        dose of 1 mg to 15 mg nicotine, e.g., 5-10 mg nicotine, e.g.,        about 8 mg nicotine, wherein the weight of the nicotine is        calculated as the free base equivalent, irrespective of whether        the nicotine is in free base or salt form.    -   1.40. Any foregoing formulation wherein the weight of the        contents of the pouch is from 0.2 g to 1 g, e.g. from 0.3 g to        0.5 g, e.g., about 0.4 g.    -   1.41. Any foregoing formulation when made according to any of        Methods 1, et seq.    -   1.42. Any foregoing formulation for use in a method of        delivering nicotine to a subject, e.g. a person in need of        nicotine replacement therapy.    -   1.43. Any foregoing formulation wherein the formulation has a        shelf life of at least 6 months, e.g. at temperatures up to 40°        C.    -   1.44. Any foregoing formulation wherein the formulation has a pH        of less than 7, e.g., pH 5.5 to pH 6.9, e.g., about pH 6.5, when        measured in a 10% slurry in water, and exhibits improved        stability, mouth feel, and/or flavor relative to a product        having a pH of at least 8 when measured in a 10% slurry in        water.

In another embodiment, the disclosure provides a method (Method 1) ofmaking a chewable nicotine formulation, e.g., according to any ofFormulation 1 above, comprising the steps of

-   -   a) dissolving nicotine and an orally-acceptable acid in a        non-aqueous orally-acceptable solvent,    -   b) adding flavor components,    -   c) mixing with solid orally-acceptable binder and optionally a        salt, and    -   d) filling a water-permeable, water-insoluble pouch with the        mixture thus obtained.        For example, Method 1 comprises    -   1.1. Method 1 wherein the orally-acceptable acid is selected        from hydrochloric acid, tartaric acid, pyruvic acid, phosphoric        acid, salicylic acid, malic acid, carbonic acid, acetic acid,        citric acid, tartaric acid, folic acid, fumaric acid, lactic        acid, and benzoic acids.    -   1.2. Any foregoing method wherein the orally-acceptable acid is        an organic acid.    -   1.3. Any foregoing method wherein the orally-acceptable acid is        a monoprotic organic acid.    -   1.4. Any foregoing method wherein the orally-acceptable acid is        benzoic acid.    -   1.5. Any foregoing method wherein the molar ratio between        nicotine and orally-acceptable acid in step a) is from 3:1 to        1:3, e.g., from 2:1 to 1:1.    -   1.6. Any foregoing method wherein the molar ratio between        nicotine and orally-acceptable acid in step a) is about 3:2.    -   1.7. Any foregoing method wherein the orally acceptable acid is        benzoic acid, and the weight ratio of weight ratio of nicotine        to benzoic acid in step a) is 1:1 to 3:1, e.g., about 2:1.    -   1.8. Any foregoing method wherein the nonaqueous solvent        comprises propylene glycol, e.g. wherein the nonaqueous solvent        is propylene glycol.    -   1.9. Any foregoing method wherein the nonaqueous solvent is        heated to facilitate dissolution of the nicotine and the        orally-acceptable acid.    -   1.10. Any foregoing method wherein the binder is selected from        polysaccharides, polyols, sugars, natural fibers,        microcrystalline cellulose, cellulose and cellulose derivatives,        and mixtures thereof.    -   1.11. Any foregoing method wherein the binder is a hydroscopic        but insoluble material.    -   1.12. Any foregoing method wherein the binder comprises        microcrystalline cellulose.    -   1.13. Any foregoing method wherein the water-permeable, water        insoluble pouch is made of a semi-permeable material which        substantially prevents the binder from leaving the bag but        permits saliva and therein dissolved components from the powder        in the pouch to freely pass through said material.    -   1.14. Any foregoing method wherein the water-permeable, water        insoluble pouch is made from one or more polymers or fibers safe        for oral use, e.g., selected from polypropylene, low density        polyethylene, polyethylene terephthalate, polyurethane,        polyvinyl acetate, polyvinyl alcohol, polystyrene,        poly(ethylene-vinyl acetate), rayon, silk, cotton, polyester,        cellulosic materials (e.g., hydroxypropyl cellulose), and        combinations thereof.    -   1.15. Any foregoing method further comprising adding one or more        additional components selected from antioxidants, emulsifiers,        preservatives, and solvents.    -   1.16. Any foregoing method further comprising adding to the        binder a neutral alkali salt, e.g., selected from sodium        chloride, potassium chloride, and mixtures thereof, e.g.,        potassium chloride.    -   1.17. Any foregoing method wherein no basic ingredient is added        other than nicotine.    -   1.18. Any foregoing method wherein all steps are carried out        under substantially water-free conditions.    -   1.19. Any foregoing method wherein the product of step b) has an        apparent pH of 5 to less than 7, e.g. about 5.5-6.5, when        measured using a pH-sensitive glass electrode concentrically        surrounded by a reference electrode filled with reference        electrolyte, which measures the H⁺ ion concentration of the        solution.    -   1.20. Any foregoing method, wherein the product of step c) has a        pH of less than 7, e.g., pH 5.5 to pH 6.9, e.g., about pH 6.5,        in a 10% slurry in water.    -   1.21. Any foregoing method, wherein the ratio by weight of (i)        binder and (if present) neutral alkali salt, e.g., potassium        chloride, to (ii) nicotine, nicotine benzoate, propylene glycol,        and flavor in the product of step c) is from 70:30 from 50:50,        e.g., 65:35 to 55:45, e.g. about 60:40.    -   1.22. Any foregoing method wherein the product of step c)        consists of nicotine, nicotine benzoate, potassium chloride,        propylene glycol, flavor, and binder.    -   1.23. Any foregoing method wherein the product of step c)        consists of nicotine, nicotine benzoate, potassium chloride,        propylene glycol, flavor, and microcrystalline cellulose.    -   1.24. Any foregoing method wherein the flavor components are pH        neutral.    -   1.25. Any foregoing method wherein the flavor components        comprise one or more flavors selected from mint oil, menthol,        watermelon, blueberry, pomegranate, strawberry, blueberry,        dragonfruit, and cucumber flavors.    -   1.26. Any foregoing method wherein the flavor components        comprise mint oil and/or menthol.    -   1.27. Any foregoing method wherein the nicotine comprises        synthetic nicotine. 1.28. Any foregoing method wherein the        nicotine comprises nicotine from tobacco.    -   1.29. Any foregoing method wherein the nicotine has an (R):(S)        isomeric ratio of greater than 1.    -   1.30. Any foregoing method wherein the product of step c) in dry        powder form.    -   1.31. Any foregoing method wherein the product of step c)        comprises 2-5%, e.g., 2.5-3.5%, of nicotine and nicotine salts,        by weight.    -   1.32. Any foregoing method wherein the product of step c)        comprises 4-20%, e.g., 5%-15%, e.g., about 5%, or about 10%, or        about 15%, of propylene glycol, by weight.    -   1.33. Any foregoing method wherein the product of step c)        comprises 50%-70%, e.g. 55%-60%, of microcrystalline cellulose,        by weight.    -   1.34. Any foregoing method wherein the product of step c)        comprises 0.5%-2%, e.g., 1%-1.5%, of potassium chloride, by        weight.    -   1.35. Any foregoing method wherein:        -   in step a), the amount of nicotine is 1% to 3%, e.g., 2%,            the orally-acceptable acid is benzoic acid in an amount of            0.5% to 1.5%, e.g., 1%, and the non-aqueous            orally-acceptable solvent is propylene glycol, in an amount            of 5% to 20%;        -   in step b), the amount of flavor components is 20% to 35%;            and        -   in step c), the solid binder is microcrystalline cellulose            in the amount of 55% to 60% and a salt is present which is            potassium chloride in the amount of 1% to 1.5%;        -   wherein all amounts are given by weight of the product of            step c).    -   1.36. The foregoing method wherein the weight percent of the        microcrystalline cellulose plus the potassium fluoride is 55% to        65% and the weight percent of the propylene glycol plus the        flavor is 35% to 40%.    -   1.37. Any foregoing method wherein in step d), each pouch is        filled with a mixture of the product of step c) containing 1 mg        to 10 mg nicotine (weight given as free base equivalent).    -   1.38. Any foregoing method, wherein the product is any of        Formula 1, et seq.

In a further embodiment, the disclosure provides a method of deliveringnicotine to a subject comprising administering a chewable nicotineformulation according to any of Formulation 1, et. seq. to the subject,e.g., a needed, e.g., up to 3× daily, e.g., wherein the subject is apatient in need of nicotine replacement therapy.

Example 1: Nicotine Pouch Formulations

Formulation A—The following components are combined as described above:

Name of Material Absolute Quantity (% w/w) Nicotine 2.00% Benzoic acid2.00% Propylene glycol 14.40% Flavor Mix 21.60% MCC 58.84% PotassiumChloride 1.16% Total 100%

The propylene glycol is heated in a heated mixing tank to 70-SC. Benzoicacid is added and mixed until it completely dissolves. Then nicotine isadded and mixed well. Flavor components are added one by one and mixedto form a liquid premix. Microcrystalline cellulose (MCC) and potassiumchloride are mixed in a ribbon blender, then the liquid premix mixtureis added to the microcrystalline cellulose (MCC) and potassium chloridein the ribbon blender and all ingredients are mixed well, to form apowder. The powder is then measured to provide the desired dose ofnicotine and placed in pouches.

Formulation B—The following components are combined as described above:

Name of Material Absolute Quantity (% w/w) Nicotine 2.00% Benzoic acid2.00% Propylene glycol 4.00% Flavor Mix 32.00% MCC 58.84% PotassiumChloride 1.16% Total 100%

Formulation C—The following components are combined:

Name of Material Absolute Quantity (% w/w) Nicotine 2.00% Benzoic acid1.00% Propylene glycol 5.00% Flavor Mix 32.00% MCC 58.84% PotassiumChloride 1.16% Total 100%

Formulation D—The following components are combined as described above:

Name of Material Absolute Quantity (% w/w) Nicotine 2.00% Benzoic acid1.00% Propylene glycol 15.40% Flavor Mix 21.60% MCC 58.84% PotassiumChloride 1.16% Total 100%

Formulation E—The following components are combined as described above:

Name of Material Absolute Quantity (% w/w) Nicotine  2.00% Benzoic acid 1.00% Propylene glycol 15.40% Flavor Mix 21.60% MCC   60% Total 100%

Formulation F—The following components are combined as described above:

Name of Material Absolute Quantity (% w/w) Nicotine  2.00% Benzoic acid 1.00% Propylene glycol  5.00% Flavor Mix 32.00% MCC   60% Total 100%

Example 2: Nicotine Pouch Formulation Performance

The liquid premixes for Formulations C, D, E and F have an apparent pHof about 6.5, while the liquid premixes for Formulations A and B have anapparent pH of about 5.5, when measured using a standard pH sensor(i.e., a pH-sensitive glass electrode concentrically surrounded by areference electrode filled with reference electrolyte, which measuresthe H⁺ ion concentration of a solution). Note that while thismeasurement is not a true pH, as the liquid premixes are non-aqueous, itprovides a useful measure of comparative proton activity.

Formulations A and B, having higher levels of benzoic acid, are testedand found to have inferior mouth feel relative to Formulations C and D.Formulations C and D provide a “tingling” sensation, which is preferredby users.

Formulations C and D, which have potassium chloride, are found toprovide a fresher, cleaner taste compared to Formulations E and F, whichdo not contain potassium chloride.

Various solvents are tested, including other alcohols. Propylene glycolis preferred over other solvents, as it is found to dissolve both theacid and the nicotine efficiently and without excessive heating, whichis important, as heating can cause the nicotine to volatilize and cangenerate toxic fumes.

1. A chewable nicotine formulation comprising nicotine free base, anorally-acceptable nicotine salt, an orally-acceptable alcohol, flavorcomponents, and an orally-acceptable binder in a water-permeable,water-insoluble pouch, wherein the orally acceptable alcohol ispropylene glycol, and wherein the chewable nicotine formulation issubstantially free of tobacco material, and further wherein theorally-acceptable nicotine salt is prepared by dissolving nicotine freebase and an orally-acceptable acid in the propylene glycol.
 2. Theformulation of claim 1 wherein the orally-acceptable nicotine salt isnicotine benzoate.
 3. The formulation of claim 1, wherein the molarratio between nicotine free base and orally-acceptable nicotine salt isabout 1:2.
 4. (canceled)
 5. The formulation of claim 1, wherein thebinder comprises microcrystalline cellulose.
 6. The formulation of claim1, further comprising a neutral, orally-acceptable mineral salt.
 7. Theformulation of claim 1, which is substantially free of any basicingredient other than nicotine.
 8. The formulation of claim 1, which ismade under substantially water-free conditions.
 9. The formulation ofclaim 1, wherein the contents of the water-permeable, water-insolublepouch have a pH of less than 7, when measured in a 10% slurry in water.10. The formulation of claim 1, wherein the ratio by weight of (i)binder and (if present) neutral orally-acceptable mineral salt, to (ii)nicotine, orally-acceptable nicotine salt, orally-acceptable alcohol,and flavor, is from 70:30 to 50:50.
 11. The formulation of claim 1,wherein the orally-acceptable nicotine salt is nicotine benzoate, theorally-acceptable alcohol is propylene glycol, and the orally-acceptablebinder is microcrystalline cellulose.
 12. The formulation of claim 1,wherein the contents of the water-permeable, water-insoluble pouch arein dry powder form.
 13. The formulation of claim 1 comprising 1%-9% ofnicotine and orally-acceptable nicotine salts; 4% to 20% oforally-acceptable alcohol; 50%-70% of binder; 0.5%-2% oforally-acceptable mineral salt, wherein all percentages are by weight ofthe contents of the water-permeable, water-insoluble pouch.
 14. Theformulation of claim 1, wherein the contents of the water-permeable,water-insoluble pouch comprise: a. Nicotine: 1% to 6% b. Benzoic acid:0.5% to 3% c. Propylene glycol: 5% to 20% d. Flavor: 20% to 35% e.Microcrystalline cellulose: 55% to 60% f. Potassium chloride: 1% to 1.5%wherein all amounts are by weight of the contents of thewater-permeable, water-insoluble pouch, wherein the nicotine and benzoicacid are in free or salt form or mixtures thereof, and wherein theweight of the nicotine is calculated as the free base equivalent and theweight of the benzoic acid is calculated as the free acid equivalent,irrespective of the actual proportions of nicotine and benzoic acid infree or salt form.
 15. The formulation of claim 14 wherein the weightpercent of the solid components comprising microcrystalline celluloseand potassium chloride is 55% to 65%; and the weight percent of theliquid components comprising propylene glycol, nicotine, benzoic acidand flavor is 35% to 45%.
 16. The formulation of claim 14 wherein theweight ratio of nicotine to benzoic acid is 1:1 to 3:1.
 17. Theformulation of claim 1, wherein each pouch contains a dose of 1 mg to 15mg nicotine, wherein the weight of the nicotine is calculated as thefree base equivalent, irrespective of whether the nicotine is in freebase or salt form.
 18. A method of making a chewable nicotineformulation according to claim 1, comprising the steps of a) dissolvingnicotine and an orally-acceptable acid in a non-aqueousorally-acceptable solvent, b) adding flavor components, c) mixing withsolid binder and optionally a salt, and d) filling a water-permeable,water-insoluble pouch with the mixture thus obtained.
 19. A method ofdelivering nicotine to a subject comprising administering a chewablenicotine formulation according to claim 1 to the subject, wherein thesubject is a patient in need of nicotine replacement therapy.